# Developing HIV Resistant Hematopoietic Stem Cells through Targeted Base Editing

> **NIH NIH F31** · HARVARD UNIVERSITY · 2024 · $41,403

## Abstract

PROJECT SUMMARY/ABSTRACT:
 Since its emergence, the Human Immunodeficiency Virus (HIV) has infected 84 million people worldwide
and led to the deaths of 40 million people1. Despite the development of over 20 different treatment options, there
is still no cure available. As a result, many individuals infected with HIV experience long-term side effects from
antiretroviral therapy and have more comorbidities earlier in their lives than those who are not infected2,3.
Therefore, there is a need to further research alternative ways to reduce or prevent HIV infection. The two
coreceptors for HIV infection, CCR5 and CXCR4, which play an essential role in HIV infecting CD4 cells, are
promising opportunities to limit HIV. While elimination of CCR5 in hematopoietic cells is being pursued, it is clear
that CCR5-null hematopoietic cells can still be infected by CXCR4-tropic forms of HIV. Therefore, I seek to
develop HIV resistant hematopoietic stem cells by targeting both of the CCR5 and CXCR4 co-receptors
with base editing to prevent HIV entry while not impairing central functions of these proteins in
hematopoiesis.
 My first AIM will use a base editor screen to identify CCR5 mutants that knock out CCR5 expression but
also decrease the cell surface expression of CXCR4, which has been seen with other CCR5 mutants. The
results of the screen will be analyzed with fluorescence-activated cell sorting (FACS) and single cell DNA
sequencing. My second AIM will also use a base editor screen to identify CXCR4 mutants that prevent the
binding of the HIV surface proteins, but allow for the binding of the natural ligand. These CXCR4 mutants will
be tested with HIV pseudoviruses to identify mutations that prevent viral infection of the cells and a transwell
migration assay to identify mutants that maintain CXCR4 responsiveness. Single cell DNA sequencing will be
run on the cells that pass both of these tests to identify mutation candidates that meet the goals of this AIM.
 The Sankaran lab has extensive expertise in base editor screens and hematopoiesis. To complement
this skill set I have contacted other faculty in the area, such as Dr. Alajandro Balazs, to assist with any HIV related
questions I have and assist with the production of HIV pseudoviruses to test the hits from my base editor screens.
My training plan focuses on gaining further expertise in hematopoiesis, HIV biology, DNA sequencing, processing
of sequencing data, written and oral scientific communication, and scientific mentoring. With access to the Broad
Institute of MIT and Harvard, Boston Children’s Hospital, and Harvard University I have all the tools, resources,
and access to expertise necessary to excel in my research.

## Key facts

- **NIH application ID:** 11006788
- **Project number:** 1F31AI186590-01
- **Recipient organization:** HARVARD UNIVERSITY
- **Principal Investigator:** Samantha JOUBRAN
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $41,403
- **Award type:** 1
- **Project period:** 2024-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11006788

## Citation

> US National Institutes of Health, RePORTER application 11006788, Developing HIV Resistant Hematopoietic Stem Cells through Targeted Base Editing (1F31AI186590-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/11006788. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*